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To assess the accuracy of targeted and systematic biopsies for the detection of prostate cancer (PCa) and clinically significant PCa (csPCa) in the everyday practice, evaluating the need for additional systematic biopsies at the time of targeted biopsy.From our multicentric database gathering data on 2,115 patients who underwent fusion biopsy with Koelis™ system between 2010 and 2017, we selected 1,119 patients who received targeted biopsies (a median of 3 for each target), followed by systematic sampling of the prostate (12 to 14 cores). Overall and clinically significant cancer detection rate (CDR) of Koelis™ fusion biopsies were assessed, comparing target and systematic biopsies. Secondary endpoint was the identification of predictors of PCa detection.The CDR of targeted biopsies only was 48% for all cancers and 33% for csPCa. The performance of additional, systematic prostate sampling improved the CDR of 15% for all cancers and of 12% for csPCa. PCa was detected in 35%, 69%, and 92% of patients with lesions scored as PI-RADS 3, 4 and 5, respectively. Elevated PI-RADS score and positive digital rectal examination were predictors of PCa, whereas biopsy-naïve status was associated with csPCa.In the everyday practice target biopsy with Koelis™ achieves a good CDR for all PCa and csPCa, which is significantly improved by subsequent systematic sampling of the prostate. The outstanding outcomes of fusion biopsy are confirmed also in biopsy-naïve patients. Elevated PI-RADS score and positive digital rectal examination are strongly associated with presence of PCa.